The present invention relates to a series of new penem-3-carboxylic acid derivatives having valuable antibacterial activity and relatively low toxicity, and to processes for the preparation of these compounds.
The penicillins form a well-known class of antibiotics, which have found considerable use in human and animal therapy for many years. Indeed, benzyl penicillin, which was the first of the antibiotics to come into general therapeutic use, is still widely used today. Chemically, the penicillins have in common a .beta.-lactam-type structure commonly referred to as "penam", which has the following formula: ##STR3##
However, although the penicillins still form a valuable weapon in the pharmaceutical armoury the development of new, and often penicillin-resistant, strains of pathogenic bacteria has increasingly made it necessary to search for new types of antibiotic. Recently, some interest has been shown in compounds having a penem structure, that is compounds having a double bond between the carbon atoms in the 2- and 3-positions of the basic penam structure. The penem structure is as follows: ##STR4##
These penam and penem structures form the basis for the semi-systematic nomenclature of the penicillin derivatives and this nomenclature is generally accepted by those skilled in the art throughout the world and is used herein, the numbering system being that illustrated on the above structures.
A variety of penem derivatives has been disclosed in recent years, for example in U.S. Pat. No. 4,168,314 (assigned to Merck & Co.), British Pat. No. 2,013,674 (Ciba Geigy) and British Pat. No. 2,048,261 (Sankyo).
The compound disclosed in United Kingdom Pat. No. 2,048,261, namely 2-[(2-aminoethyl)thio]-6-(1-hydroxyethyl)penem-3-carboxylic acid, was considered to be of considerable interest, since it showed excellent activity against a wide variety of bacteria and thus showed considerable potential for use as an antiobiotic. However, this compound was subsequently shown to have a relatively high acute toxicity.
We have now surprisingly discovered a series of related compounds, which not only have superior antibacterial activity, but which also have a significantly lower acute toxicity.